• Journal of Life Science
• /
• v.23 no.11
• /
• pp.1404-1408
• /
• 2013

(-)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has been shown to have strong antibacterial, antiviral, antioxidant, anti-inflammatory, and chemopreventive effects. However it is unknown whether EGCG can recover alcohol-associated pancreatitis. The aim of this study was to investigate the effects of EGCG on pancreatic enzyme activities and the expressions of pancreatic regenerating related markers, such as adenosine monophosphate-activated protein kinase (AMPK), raf-1 kinase inhibitor protein (RKIP), and Regenerating gene 1 (Reg1), in mice pancreatic primary acinar cells. Our results revealed that activities of ${\alpha}$-amylase and chymotrypsin were significantly increased in the cells treated with ethanol compared to the untreated control cells; however, the increased activities of both enzymes were markedly reduced by pretreatment with EGCG. Phosphorylation of AMPK and total expression of RKIP were decreased in the ethanol-treated primary acinar cells; however, these were both significantly increased in the EGCG-pretreated cells. In addition, when EGCG was treated, expression of Reg1 was markedly increased compared with that of the control or the ethanol-treated primary acinar cells, demonstrating that EGCG can modulate pancreatic regenerating related genes. Therefore, our findings suggest that EGCG may have therapeutic utility in the prevention or treatment of alcohol-associated pancreatitis.

• Journal of Korean Medicine for Obesity Research
• /
• v.22 no.1
• /
• pp.30-37
• /
• 2022

Objectives: Adipogenesis is the process by which pre-adipocytes are differentiated into adipocytes. It also plays an important role in adipocyte formation and lipid accumulation. Ranunculus sceleratus (R. sceleratus) extracts are used for the treatment of various diseases such as hepatitis, jaundice, and tuberous lymphadenitis in oriental medicine. However, its effect on adipogenesis has not yet been studied. In this study, we investigated the effects of R. sceleratus on adipogenesis in 3T3-L1 cells. Methods: Cells were treated with 50, 100, and 200 ㎍/ml of R. sceleratus and cell viability was evaluated. To differentiate the 3T3-L1 preadipocytes, a 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI) solution were used. The accumulation of lipid droplets was determined by Oil Red O staining. The expression levels of adipogenesis-related proteins were also determined. Results: MDI solution differentiated the preadipocytes into adipocytes and accumulation of lipids was observed in the differentiated 3T3-L1 cells. Interestingly, the amount of lipid droplets was reduced after R. sceleratus treatment. In addition, the expression levels of key adipogenic transcription factors, such as CCAAT/enhancer-binding proteins-𝛼 (C/EBP-𝛼) and peroxisome proliferator-activated receptors-𝛾 (PPAR-𝛾) were also reduced after R. sceleratus treatment. Furthermore, R. sceleratus increased AMP-activated kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein-1 expression. Conclusions: Our results showed that R. sceleratus reduced preadipocyte differentiation by inhibiting C/EBP-𝛼 and PPAR-𝛾 levels via the AMPK pathway. Therefore, we suggest that R. sceleratus may be potentially used as an anti-adipogenic agent.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.4
• /
• pp.379-389
• /
• 2018

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines $TNF-{\alpha}$ and IL-6 and inflammatory lipid mediators, prostaglandin $E_2$ and leukotriene $B_4$. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed $I{\kappa}B$ phosphorylation, nuclear translocation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-13 and also hindered phosphorylation of $NF-{\kappa}B$ and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of $TNF-{\alpha}$ and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.

• Journal of Acupuncture Research
• /
• v.28 no.1
• /
• pp.1-14
• /
• 2011

목적 : 인진약침이 고지방식이로 유발된 비만 ICR mice에서 비만 및 동반 대사이상에 미치는 효과와 그 기전을 연구하고자 한다. 방법 : 인진약침의 비만 예방효과를 검증하기 위하여, 4주간 고지방식이를 급여하면서 150mg/kg 또는 300mg/kg의 인진약침을 양측 비수($BL_{20}$)에 교대로 매일 피하에 시술하였다. 또한 인진약침의 비만 치료효과를 검증하기 위하여, 4주간 고지방식이를 급여한 비만 ICR mice에 추가 4주간 고지방식이를 유지하면서 300 mg/kg 인진약침액과 vehicle control로써 등량의 distilled water를 양측 비수($BL_{20}$)에 교대로 매일 피하에 약침시술하였다. 인진약침의 항비만효과와 기전을 알아보기 위해, 체중, blood glucose, insulin, total cholesterol, triglyceride, non-esterified fatty acid (NEFA), AST, ALT levels 등 대사지표를 측정하고 부고환조직의 조직학적 관찰을 시행하였으며, AMPK activation과 adipocyte differentiation, fatty acid ${\beta}$-oxidation 및 thermogenesis와 관련된 gene expressions을 평가하였다. 결과 : 인진약침의 치료를 통하여 고지방식이 급여로 인한 체중의 증가가 억제되었을 뿐만 아니라, 비만 ICR mice의 체중을 감소시켰으며, glucose 및 lipid homeostasis를 개선시켰으며 지방조직의 증식을 억제하였다. AMPK의 phosphorylation과 CPT-1 및 UCP2의 발현을 증가시켰으며, PPAR-${\gamma}$, C/EBP${\alpha}$, aP2, LPL,FAS, SCD-1의 발현을 억제하였다. 결론 : 인진약침은 고지방식이 유도 동물모델에서 비만 및 동반 대사이상을 개선시키는 효과가 있으며, 이는 식이억제에 의한 2차적 효과라기 보다는 energy expenditure를 증가시키고, pre-adipocyte differentiation 및 proliferation을 억제하며, lipogenesis를 억제하고 lipolysis를 증가시키는 효과에 의한 것으로 사료된다.

• Nutrition Research and Practice
• /
• v.11 no.3
• /
• pp.180-189
• /
• 2017

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta ($GSK-3{\beta}$) expression levels. The ${\alpha}-glucosidase$ inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through $HNF-1{\alpha}$ expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and $GSK-3{\beta}$, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of ${\alpha}-glucosidase$ inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.

• Korean Journal of Food Science and Technology
• /
• v.52 no.1
• /
• pp.81-88
• /
• 2020

The biological activities of Platycodon grandiflorum (PG) root extracts have been studied intensively, whereas there are limited number of studies on PG seed extract (PGSE). PGSE was prepared by ethanol extraction, and its antidiabetic effect was evaluated in mice with type 2 diabetes (C57BLKS/J-db/db). Results indicated that the administration of high-dose PGSE (600 mg/kg, wb) significantly stabilized the blood glucose levels, as evidenced by the results of the oral glucose tolerance test. Mice treated with high-dose PGSE exhibited significantly lower serum hemoglobin A1c, insulin, and leptin levels after eight weeks of feeding trial (p<0.05). High-dose PGSE administration significantly improved glucose uptake in the femoral muscle of db/db mice by activating both IRS-1/PI3K/AKT/AS160 and AMPK phosphorylation pathways. GLUT4 translocation from the cytosol to the plasma membrane increased 1.7-fold in the PGSE high-dose group. These results suggest that PGSE has potential for development as an antidiabetic agent.

• Biomolecules & Therapeutics
• /
• v.20 no.2
• /
• pp.220-225
• /
• 2012

To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyperglycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes.

• Nutrition Research and Practice
• /
• v.15 no.5
• /
• pp.568-578
• /
• 2021

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 ㎍/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor 𝛄 (PPAR𝛄), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

• Herbal Formula Science
• /
• v.30 no.4
• /
• pp.269-280
• /
• 2022

Objectives : In this study, it was investigated the effects of solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis extract (PS) and its action mechanism on dexamethasone-induced muscle atrophy in mice. Methods : In mice, muscle atrophy model was induced by dexamethasone (5 mg/kg, I.p) once daily for 2 weeks and with PS extract administration (100 and 300 mg/kg, p.o.) as treatment groups. The changes in body weights, grip strength, Treadmill test, muscle weights, and the expression of atrophy-related genes were measured in muscle atrophy mice. The histological changes of gastrocnemius tissues were also observed by H&E staining with measurement of myofiber size. Results : The administration of PS extract increased significantly body weights, grip strength, treadmill test and muscle weights in muscle atrophy mice. PS extract administration increased significantly the area of myofibers and inhibited structural damages of muscle and increased significantly the expression of myogenin and decreased significantly the expression of MuRF1, Atrogin1 and phosphorylation of AMPK and PGC1α in muscle tissues of muscle atrophy mice. Conclusions : These results indicate that PS extract has a improvement effects on muscle atrophy with stimulation of myogenic differentiation and inhibition of mRNA degradation that could be related with the activation of AMPK and PGC1α signaling pathways in muscle. This suggests that PS extract can apply to treat muscle atrophy in clinics.

• The Korea Journal of Herbology
• /
• v.29 no.4
• /
• pp.77-82
• /
• 2014

Objectives : The effects of ethanol extract of Plantago asiatica L. were investgated on adipocyte differentiation, lipopogenesis, lipolysis and apoptosis using differnentiated 3T3-L1 adipocytes. Methods : Plantago asiatica L. was extracted with ethanol (CCE). We carried on MTT assay for cell proliferation, Oil Red O staining for determination of cell differentiation and intracelluar adipogenesis. TUNEL staining assay for cell apoptosis, and Western blot analysis for measurement of pAMPK and pACC, $C/EBP{\alpha}$, $PPAR{\gamma}$ protein expressions were performed. Results : The addition of CCE up to 0.2 mg/ml into cell culture media showed no cytotoxicity. Treatment of 0.2 mg/ml CCE significantly inhibited differentiation in 3T3-L1 preadipocytes. Lipid accumulation of the CCE treated cells was decreased compared with that of control. Induction of cell apoptosis was increased in CCE treated cells compared with that of control. AMPK and ACC levels of the cells with 0.2 mg/ml CCE were led to phosphorylation and also expressions of $C/EBP{\alpha}$ and $PPAR{\gamma}$, as adipogenic transcription factors, were suppressed compared with those of control. Conclusions : Taken together, these results provide evidence that CCE has a regulatory role in lipid metabolism that is related to differentiation into adipocytes, adipogenesis and apoptosis.